Heart valve leaflet replacement systems and methods for using them

ABSTRACT

A prosthetic heart valve for treatment of a diseased heart valve having native anterior and posterior leaflets that move between an open configuration and a closed position to regulate blood flow through the heart valve during a cardiac cycle of a heart. The prosthetic heart valve having a crescent shaped stent, at least one prosthetic leaflet mounted on an inner surface of the stent, and at least one prong structure coupling a portion of the at least one prosthetic leaflet to a lower ventricular portion of the stent frame. The prosthetic heart valve further having systems for anchoring the upper flared portion of the stent to a posterior portion of the native valve annulus.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of co-pending application Ser. No.15/453,518, filed Mar. 8, 2017, issuing as U.S. Pat. No. 11,007,057,which claims benefit of U.S. provisional applications Ser. Nos.62/305,204, filed Mar. 8, 2016, 62/413,693, filed Oct. 27, 2016, and62/427,551, filed Nov. 29, 2016, the entire disclosures of which areexpressly incorporated by reference.

FIELD

The application relates generally to replacement heart valves,preferably for replacing diseased mitral and/or tricuspid valveleaflets. More particularly, embodiments of the subject matter relate totissue-based replacement heart valves and systems and methods tooperatively deliver the replacement valve.

BACKGROUND

Referring to FIG. 1, the mitral valve (MV) sits between the left atrium(LA) and the left ventricle (LV) of a human heart and normally consistsof a mitral annulus (MA), two leaflets, chordae tendineae (“chords”),two papillary muscles, and the left ventricular myocardium. The mitralannulus is subdivided into an anterior portion and a posterior portion.Normally, the anterior mitral leaflet (AML) is connected to the aorticvalve via the aortic-mitral curtain, and the posterior mitral leaflet(PML) is hinged on the posterior mitral annulus. The chords originatefrom either the two major papillary muscles (PPM) or from multiple smallmuscle bundles attaching to the ventricular wall and connect to the freeedge of the mitral leaflets. Chords are composed mainly of collagenbundles, which give the chords high stiffness and maintain minimalextension to prevent the leaflets from billowing into the left atriumduring systole. Furthermore, a normal mitral valve consists of right andleft trigones, which are two thickened regions that consist of fibroustissues. The right fibrous trigone is between the aortic ring and theright atrioventricular ring and the left fibrous trigone is between theaortic ring and the left atrioventricular ring.

When the mitral valve is closed, the respective anterior and posteriorleaflets are in close contact to form a single zone of apposition. Asone skilled in the art will appreciate, normal mitral valve functioninvolves a proper force balance, with each of its components workingcongruently during a cardiac cycle. Pathological alterations affectingany of the components of the mitral valve, such as chord rupture,annulus dilatation, papillary muscle displacement, leafletcalcification, and myxomatous disease, can lead to altered mitral valvefunction and cause mitral valve regurgitation (MR).

Mitral regurgitation is dysfunction of the mitral valve that causes anabnormal leakage of blood from the left ventricle back into the leftatrium during systole (i.e., the expulsion phase of the heart cycle inwhich blood moves from the left ventricle into the aorta). While trivialmitral regurgitation can be present in healthy patients, moderate tosevere mitral regurgitation is one of the most prevalent forms of heartvalve disease. The most common causes of mitral regurgitation includeischemic heart diseases, non-ischemic heart diseases, and valvedegeneration. Both ischemic (mainly due to coronary artery diseases) andnon-ischemic (idiopathic dilated cardiomyopathy for example) heartsdiseases can cause functional, or secondary, mitral regurgitationthrough various mechanisms, including impaired left ventricle wallmotion, left ventricle dilatation, and papillary muscle displacement anddysfunction. In functional mitral regurgitation, the mitral valveapparatus remains normal. Incomplete coaptation of the leaflets is dueto enlargement of the mitral annulus secondary to left ventricledilation and possibly left atrium enlargement. In addition, patientswith functional mitral regurgitation can exhibit papillary muscledisplacement due to the left ventricle enlargement, which results inexcessive tethering of the leaflets. In contrast, degenerative (ororganic) mitral regurgitation is caused by structural abnormalities ofthe mitral leaflets and/or the subvalvular apparatus, which can includestretching or rupture of tendinous chords.

The current treatments for mitral valve diseases include surgical repairand replacement of the mitral valve. Mitral valve repair, benefitingfrom improved understanding of mitral valve mechanics and function, maybe now preferred to complete mitral valve replacement. However, thecomplex physiology and three-dimensional anatomy of the mitral valve andits surrounding structure present substantial challenges when performingthese repair procedures.

In one early example of a transcatheter mitral valve replacement device,

Endovalve-Herrmann (Micro Interventional Devices, Inc.), developed amitral prosthesis that had a foldable Nitinol-based valve with a sealingskirt. Similarly, Tendyne Holdings, Inc. produces a prosthetic mitralvalve replacement device comprising bovine pericardium with aself-expandable Nitinol stent. The device is designed for transapicaldelivery and has a ventricular fixing anchor. CardiAQ uses bovinepericardium with a Nitinol self-expandable stent in their mitral valvereplacement device. Finally, Tiara (Neovasc, Inc.) uses a mitral valvereplacement system that is deliverable trans-apically with a 30 Frcatheter that has anchor structures, and bovine pericardium on aself-expandable stent with a D-shaped atrial portion and a ventricularportion that has an outer coating. These devices and the techniques todeliver the mitral prosthesis into the operative position are still atdevelopment stages and, though promising, challenges to the efficacy ofthese devices continue to exist.

The noted challenges to an efficacious mitral valve replacement devicegenerally include operative delivery challenges; positioning andfixation challenges; seal and paravalvular leakage challenges; andhemodynamic function challenges such as left ventricle outflow tract(LVOT) obstruction. With respect to the noted operative deliverychallenges, since a conventional mitral prosthetic is larger than aconventional aortic prosthesis, it is more difficult to fold andcompress the larger mitral prosthesis into a catheter for deployment aswell as retrieval through either conventional trans-apical ortrans-femoral delivery techniques.

Turning to the positioning and fixation challenges, instability andmigration are the most prominent obstacles given that the mitral valveis subjected to high and repetitive loads in a cardiac cycle, with ahigh transvalvular pressure gradient that is near zero at diastole andcan rise to 120 mmHg or more during systole and higher than 150 mmHg ofsystolic pressure for patients with aortic stenosis and systemichypertension. The lack of calcium distribution at the mitral annulusalso affects device stability and anchoring. Further, the transcathetermitral valve replacement can be easily dislodged as the heart movesduring each beating cycle.

With respect to sealing and paravalvular leakage, since the mitral valveannulus is large, a good fit between the native annulus and theprosthesis that minimizes paravalvular leak is desirable. Typically, aprosthetic mitral valve may have a large over-hanging atrial portion orflare which can prevent leakage, but, problematically, it also requiresa large valve size at the ventricular level so that the prosthesis canbe tightly fitted in the native mitral valve. Conventionally, aprosthetic mitral valve is smaller than the diseased native valve andadditional material is added around the prosthetic valve to compensatefor the large native mitral annulus. Undesirably, adding more materialto a prosthetic valve increases the size of the delivery system.

Finally, with respect to the preservation of hemodynamic function, theoperative positioning of a prosthetic mitral valve, which isconventionally large as described above, should not obstruct the LVOT atthe anterior portion of the mitral annulus and should not interfere withthe associated structures of a native mitral valve.

Accordingly, it would be beneficial to have a heart valve leafletreplacement system that does not suffer from the shortcomings anddeficiencies of conventional valve prosthetics. It is desirable tosecure the prosthetic mitral valve replacement system to the nativemitral annulus. It is also desirable to improve positioning of a mitralprosthesis and prevent leaking of blood between the mitral prosthesisand the native mitral valve. Similarly, it is desirable to preventfurther dilation of the native mitral annulus. Furthermore, otherdesirable features and characteristics will become apparent from thesubsequent detailed description and the appended claims, taken inconjunction with the accompanying drawings and the foregoing technicalfield and background.

SUMMARY

Described herein is a heart valve leaflet replacement system and amethod of securing a heart valve leaflet replacement system to one ofthe native valve annuli. It is contemplated that the method of securinga heart valve leaflet replacement system to one of the native valveannuli is configured to prevent dislodgment of the leaflet replacementsystem from the annulus and to ensure the proper coaptation between theimplanted prosthetic leaflets with the remaining native leaflets. It iscontemplated that the valve leaflet replacement device can be implantedvia an open surgical procedure or transluminally via catheter. In oneaspect, the heart valve leaflet replacement system can be configured tosecure the prosthetic mitral valve to the native mitral annulus. In afurther aspect, the associated methods can be configured to implant thereplacement valve prosthesis and to help prevent further dilation of thenative mitral annulus. For clarity, it will be appreciated that thisdisclosure will focus on the treatment of functional mitralregurgitation, however it is contemplated that the heart valve leafletreplacement system and the associated methods can be used or otherwiseconfigured to be used to treat other valve disease conditions andreplace other valves of the human heart, or could be used or otherwiseconfigured to be used in other mammals suffering from valve deficienciesas well.

In one aspect, the heart valve leaflet replacement system can comprise areplacement prosthetic mitral valve that is configurable or otherwisesizable to be crimped down to fit within a delivery sheath and tosubsequently be selectively expanded to an operative size and positiononce removed from the delivery sheath within the heart. In a furtheraspect, at least a portion of the prosthetic mitral valve can have astent shape, which can comprise an upper flared atrial portion and alower vertical ventricular portion. In one aspect, the upper flaredportion can be configured to facilitate anchoring of the stent, whichcan help prevent paravalvular leakage and dislodgement of the stent.Further, the lower ventricular portion can displace a diseased nativeleaflet out of the blood flow tract and house at least one prostheticleaflet. In another aspect, the prosthetic mitral valve can comprise alining skirt that can be coupled to at least a portion of the innerand/or outer surfaces of the stent. In one exemplary aspect, at leastone prosthetic leaflet can be mounted on the inner lumen of the stentand/or on at least a portion of the outer side of the stent, which canfunction in place of at least one native leaflet to restore normal valvefunction, e.g., to prevent mitral regurgitation.

In one aspect, at least one leaflet of the prosthetic mitral valve canhave at least one prong-shaped structure which prevents the valveleaflets from billowing into the atrium and prolapsing. The at least oneprong-shaped structure also acts to reduce prosthetic leaflet stress andfacilitate the coaptation with at least one of the native mitral valveleaflets, in order to recreate the competent closure anatomy of a nativemitral valve with sufficient leaflet coaptation length and height andproper leaflet angles during systole.

In one aspect, the delivery of the prosthetic mitral valve can beconducted using several desired delivery access approaches, such as, forexample and not meant to be limiting, a surgical approach, atrans-septal approach, a trans-atrial, or a trans-apical approach. Inone exemplary aspect, the trans-septal approach can comprise creating anopening in the internal jugular or femoral vein for the subsequentminimally invasive delivery of portions of the heart valve leafletreplacement system through the superior vena cava, which flows into theright atrium of the heart. In this exemplary aspect, the access path ofthe trans-septal approach crosses the atrial septum of the heart, andonce achieved, the components of the heart valve leaflet replacementsystem can operatively be positioned in the left atrium, the nativemitral valve, and the left ventricle. In one aspect, it is contemplatedthat a main delivery catheter can be placed therein the access path toallow desired components of the heart valve leaflet replacement systemto be operatively positioned in the left atrium without complications.

In one aspect, a plurality of fixation members can be operativelypositioned and implanted at desired locations in the native annulusprior to the delivery of the replacement prosthetic valve. In thisaspect, the fixation members can improve the subsequent positioning andanchoring of the replacement prosthetic valve. In a further aspect, theplurality of fixation members can help prevent leakage of blood betweenthe operatively positioned prosthesis and the native mitral valve.

In an exemplary aspect, the fixation members can be an anchor, havingproximal and distal portions. In a further aspect, each anchor can beoperatively inserted and embedded into the annular tissue. In oneaspect, the distal portion of the anchor can be fully embedded orpartially embedded into the annular tissue. In one aspect, the distalportion can be connected to the proximal portion of the anchor. In thisaspect, the distal portion of the anchor can be configured to receive aflexible component that acts as a bridge connecting the prosthetic valveto the anchor. In this aspect, the flexible component can be used as ameans for precisely guiding and securely maneuvering the prostheticmitral valve to the native mitral valve.

In a further aspect, the flexible component can be a tether that isconfigured so one end of the tether is attached to the proximal portionof the anchor and the other end of the tether can exit the body.Subsequently, the prosthetic mitral valve can be delivered over thetethers and positioned over the anchors such that the upper flaredportion of the stent can be in close proximity to the anchors.

In one aspect, it is contemplated that a plurality of locking devicescan be delivered through a plurality of tethers and positioned over theupper flared portion of the stent immediately following the delivery ofthe prosthetic valve. In this aspect, a portion of the tether connectedto the proximal portion of the anchor, will pass through the upperflared portion of the prosthetic valve, and enter the locking device,which will engage the tether and fixate the stent in the operativeposition against the plurality of anchors. The portion of the tetherexiting the locking device can be subsequently removed using aconventional suture-like cutting device.

Therefore, in this aspect, the delivery system for the prosthetic valvecan comprise a main deflectable delivery catheter that can house and actas a delivery pathway for the valve catheter, an assembly for deliveryof the plurality of anchors, and an assembly for delivery of theprosthetic mitral valve and plurality of locking devices.

In one aspect, the locking device can be a distinct structure from thestent and fixation members. In one exemplary aspect, the locking devicecan be configured as a tubular structure, which can clamp on to at leastone tether using one or more tabs extending radially inwards from oneside of the tubular structure and forming a tight contact against theopposite side of the tubular structure. The tethers can have inline maleprotrusions that are configured to increase friction and axialresistance to prevent tether slippage. In this aspect, the tubularlocking device can be delivered and released using a locking deliverysystem.

The locking delivery system can comprise a lock supporting catheter anda lock delivery catheter. The lock supporting catheter can comprisestiff and flexible portions. In this aspect, the stiff portion can beconfigured to open one or more tabs, i.e., push the tabs towards thewall of the locking device to allow the tether to pass through therebyfacilitating sliding of the locking device along the tether. It will beappreciated that the flexible portion of the lock supporting catheterallows the catheter to flex and bend easily which can facilitatedelivery of the locking device at different locations around theannulus. In this aspect, the locking delivery catheter can be a flexiblecatheter, which can be conventionally operated to push the lockingdevice off the stiff portion of the locking supporting catheter so thatit can release the tabs and grab onto the tether within the tubularstructure of the locking device to effectively lock it into place alongthe tether.

It is noted that a brief episode of rapid ventricular pacing (180-220beats/min) is often performed during implantation of transcatheter heartvalves to minimize transvalvular flow and thereby reduce the risk ofvalve embolization during the procedure. The amount of time used forrapid pacing is minimal, usually between 14-29 seconds to minimize riskto the patient. It is contemplated that the prosthetic mitral valve canbe deployed and secured to the native mitral valve within 25 seconds ofrapid pacing using the delivery system of the invention. Following thetranscatheter deployment of a plurality of anchors attached to tethers,the delivery system provides for precise deployment of the replacementprosthetic mitral valve, simultaneous delivery of multiple lockingdevices and secured attachment of the locking devices to the replacementprosthetic mitral valve within 25 seconds, followed by easy removal ofthe trailing tethers.

In one aspect, simultaneous delivery of multiple locking devices can beachieved using a lock housing structure. In this aspect, the lockhousing structure can be configured with multiple lumens to housemultiple locks and locking catheters. In this aspect, it will beappreciated that the lock housing structure can also be configured toload the prosthetic mitral valve onto the valve catheter. When theprosthetic mitral valve device is crimped into a smaller size and loadedonto a valve delivery catheter, the lock housing structure is loadedclosest to the tip of the upper flared portion of the replacementprosthetic mitral valve. A plurality of the locking devices and lockcatheters can be loaded into the lock housing structure, locatedadjacently to the tip of the upper flared portion of the replacementprosthetic valve, which will allow the locking devices to be deployedimmediately after the replacement prosthetic valve.

In one aspect, of the prosthetic mitral valve delivery, followingdeployment of anchors to the native annulus attached to one end of thetethers, the other end of the tethers still outside the body, can bepassed through the upper flared portion of the stent and housed withinthe lock catheters, which are then loaded into the lock housingstructure. In one aspect, housing of the tethers within the upper flaredportion of the stent and the lock catheters can be easily achieved usingthe tether supporting catheter, which can be eventually removed from thebody prior to the release of the replacement prosthetic valve.

In one optional aspect, the lock housing structure is coupled to thevalve catheter to prevent rotation between the prosthetic valvereplacement and the valve catheter. Additionally, the valve catheter canbe configured such that it will not rotate as it is advanced towards thetargeted implant location within the native mitral valve duringdelivery. One advantage of this non-rotational feature is that itprevents the tethers from being tangled within the main deflectabledelivery catheter.

Retracting the valve catheter will release the replacement prostheticvalve. In this aspect, release of the distal end of the prosthetic valvereplacement can be achieved trans-annularly. When the distal end of theprosthetic valve replacement is partially released, the entire valvecatheter can be positioned across the valve annulus. A complete valverelease can be performed during rapid pacing. The lock catheters will bereleased immediately following the release of the replacement prostheticvalve.

Release of the lock and lock catheters can be achieved by manipulatingthe two linking structures that are coupled to the lock housingstructure and the main delivery system handle. In a further aspect, onelinking structure enables simultaneous push out of the lockingcatheters, and the second linking structure, adjacent to the firstlinking structure, enables release of the locking devices onto the upperflared portion of the replacement prosthetic mitral valve.

It is contemplated that any suture-like cutting device can be used tocut the remaining tethers exiting the proximal portion of the lockingdevice. The entire delivery system can be removed, and the septalclosing device can be used to close up the hole on the atrial septum.

Various implementations described in the present disclosure can includeadditional systems, methods, features, and advantages, which can notnecessarily be expressly disclosed herein but will be apparent to one ofordinary skill in the art upon examination of the following detaileddescription and accompanying drawings. It is intended that all suchsystems, methods, features, and advantages be included within thepresent disclosure and protected by the accompanying claims.

DESCRIPTION OF THE FIGURES

The features and components of the following figures are illustrated toemphasize the general principles of the present disclosure.Corresponding features and components throughout the figures can bedesignated by matching reference characters for the sake of consistencyand clarity.

FIG. 1 is a perspective view of the anatomy of a native mitral valve,showing the location of the mitral valve (MV) in the heart.

FIGS. 2A and 2B are perspective views of an exemplary aspect of a heartvalve leaflet replacement system, showing a stent having an upper flaredportion and a lower ventricular portion, a prosthetic pronged leaflet,where the prong couples the prosthetic leaflet to the lower ventricularportion of the stent.

FIG. 3 demonstrates the circumferential dimensions of the device. Theanterior mitral leaflet is divided into three scallops: A1, A2 and A3.The posterior mitral leaflet is divided into three scallops: P1, P2 andP3. The flared portion of the device can span the two commissures,AC-anterior commissure and PC-posterior commissure, or can cover theentire circumference of the mitral valve when operatively positioned.The ventricular portion of the device can span the two commissures,covering the entire posterior portion of the mitral valve.

FIG. 4 is perspective view of the computer generated model of theprosthetic device, showing the upper flared portion and the lowerventricular portion of the stent of FIG. 2 without a skirt attached forclarity, shown in an exemplary operative position in the native mitralannulus in contact with the computer generated heart model.

FIGS. 5A and 5B are perspective views of one exemplary aspect of thestent which consists of a plurality of cell structures and the junctionsbetween adjacent cells, showing the upper flared portion, the lowerventricular portion, and the portions housing each of the prostheticleaflets. In one aspect, it is contemplated that in the upper flaredportion, the junctions or anchor openings can form bores that areconfigured to facilitate delivery of the stent into the mitral positionvia tether components. In one exemplary aspect, the bores can have asubstantially circular shape.

FIGS. 6A-6E are perspective views of exemplary stent designs. Asexemplarily shown, the heights of the lower ventricular portion of thestent can vary, particularly on the two lateral ends. Optionally, thecell structures of the lower ventricular portion of the stent can be ofdifferent shapes and dimensions.

FIGS. 7A-7C are perspective views of exemplary stent designs withadditional features to capture native leaflets. As exemplarily shown,the distal ventricular portion of the stent can have hooks, barbs,cables, and the like that extend radially to grab the surrounding nativeleaflets. The capturing components can be evenly distributed along thecircumference of the lower ventricular portion of the stent, or onlyalong the middle section of the lower ventricular portion of the stent,or only at the two ends of the lower ventricular portion of the stent.

FIGS. 8A-8E shows perspective views of exemplary stent designs withvariable height and design along the stent circumference. As exemplarilyshown in FIGS. 8A-8B, the bottom ventricular portion of the stent canhave a meshed structure, or optionally as shown in FIGS. 8C-8E, thebottom ventricular portion of the stent can have a non-meshed structure.Further, the bottom ventricular portion can be selectively configured toattach and support the at least one prosthetic leaflet as exemplaryshown in FIGS. 8C-8E.

FIGS. 9A and 9B are perspective views of an exemplary aspect of thestent where the upper flared portion covers the entire native mitralannulus, and a perspective view of the stent in the operative position.

FIGS. 10A′-10C′″ are top elevational views of exemplary aspects of aprosthetic leaflet. FIGS. 10A′-10A′″ shows prosthetic leaflets that haveat least one additional tissue or leaflet coaptation extension that areconfigured to extend from the distal free-edge of each of the prostheticleaflets (the side leaflets and the middle leaflets) and where exemplaryaspects of the prong structures are configured to be operatively coupledto leaflet coaptation extension. FIGS. 10B′-10B′″ is another exemplaryaspect of the prosthetic leaflets in which there is no prong structurefor the side leaflets, with only the middle leaflet having at least oneprong structure. FIGS. 10C′-10C′″ is another exemplary aspect of theprosthetic leaflets where the side leaflets are configured or slantedsuch that the portion of the side leaflets that are spaced away from themiddle leaflet has a shorter leaflet height when compared to the portionof the side leaflets that are adjacent to the middle leaflet. In oneaspect, the prosthetic leaflets of this example can optionally not haveany prong structures.

FIGS. 11A-11H are top elevational views of different exemplary aspectsof the prosthetic leaflet structures including belly region, free edge,and commissure regions. FIGS. 11A and 11B show an exemplary aspect wherethe prosthetic heart valve replacement consists of two leaflets. FIGS.11C-11H show an exemplary aspect where the prosthetic heart valvereplacement consists of three leaflets. Illustrated in FIGS. 11C and11D, the prosthetic leaflets can each have the same design. Optionally,illustrated in FIGS. 11E-11H, the prosthetic leaflets can have differentdesigns. Further, the prosthetic leaflets can have a uniform height, orcan have an extended free edge as illustrated in FIG. 11H to enhancecoaptation, or can have a variable height as shown in FIGS. 11G and 11H.

FIGS. 12A-12F are top elevational views of exemplary aspects of thecoaptation and strength enhancing prong structures coupled to portionsof a prosthetic leaflet, showing a plurality of prong structuresoperatively coupled to a distal free-edge, to a portion of a coaptationregion, and/or to a belly region of the respective prosthetic leaflet.

FIGS. 13A-13B are perspective views of computer generated models of aprosthetic heart valve leaflet replacement system, showing prostheticleaflets coupled to an exemplary stent, where the leaflet and stentheight is uniform along the device circumference.

FIG. 14A-14C are perspective views of computer generated models of aprosthetic heart valve leaflet replacement system, showing prostheticleaflets coupled to an exemplary stent, where the leaflet and stentheight is shorter at the sides.

FIG. 15 illustrates the prosthetic leaflet to stent attachment points inthree dimensional space for one exemplary aspect of a heart valvereplacement system where the solid dots indicate the attachment pointsfor the edges of the prosthetic leaflets and the open triangles indicatethe attachment points of the prong structures to the stent.

FIG. 16 illustrates the prosthetic leaflet to stent attachment points intwo dimensional space for one exemplary aspect of a heart valvereplacement system where the solid dots indicate the attachment pointsfor the edges of the prosthetic leaflets and the open triangles indicatethe attachment points of the prong structures to the stent.

FIG. 17 is a side elevational view of an exemplary aspect of the anchorfor the heart valve leaflet replacement system that is configured to beimplanted, showing the atrial side of the anchor having a through slotconfigured to accept a tether, and two L-shape slots on two oppositesides configured for the anchor delivery member to engage for delivery,the ventricular side of the anchor that is configured for implantation,and anchor technical specifications.

FIGS. 18A-18C are perspective views of an exemplary anchor deliverysystem. In this aspect, the anchor delivery catheter tip in FIG. 18A canbe coupled to the end of the anchor delivery catheter shown in FIG. 18C.The inner wall of the anchor delivery catheter tip can be configured tohave two pins for engaging and holding the anchor in place as shown inFIG. 18B. In this aspect, the tether can be looped through the throughslot on the atrial side of the anchor.

FIG. 19 is a perspective elevational view of an exemplary anchordelivery catheter for delivery of an anchor.

FIG. 20 is a side elevational view of an exemplary anchor for the heartvalve leaflet replacement system that is configured to be implanted,showing a means for locking the stent to the anchor coupled to a portionof a tether portion that extends from the atrial side of the anchor andshowing the ventricular side of the anchor that is configured forimplantation.

FIG. 21 is a side elevational view of an exemplary anchor for the heartvalve leaflet replacement system that is configured to be implanted,showing a means for locking the stent to the anchor coupled to a portionof a tether portion that extends from the atrial side of the anchor andshowing the ventricular side of the anchor that is configured forimplantation.

FIG. 22 is a perspective view of an exemplary anchor for the heart valveleaflet replacement system.

FIG. 23 is a perspective view of an exemplary anchor for the heart valveleaflet replacement system.

FIG. 24 is a perspective view of an exemplary anchor for the heart valveleaflet replacement system.

FIG. 25 is a cross-sectional view of an exemplary anchor delivery memberfor the heart valve leaflet replacement system, showing a portion of theanchor delivery catheter selectively coupled to a portion of the atrialside of an anchor.

FIG. 26 is a cross-sectional view of an exemplary anchor delivery memberfor the heart valve leaflet replacement system, showing a portion of theanchor delivery catheter selectively coupled to a portion of the atrialside of an anchor.

FIG. 27A-27C are partial cross-sectional side views of an anchor beingmounted at a desired location on the native mitral annulus. FIG. 27Ashows the anchor being positioned at a desired installation point on themitral annulus. FIG. 27B shows the anchor delivery member being rotatedin a first direction to fixate the anchor into the mitral annulus. FIG.27C shows the anchor delivery member being rotated in the oppositedirection to detach the implanted anchor from the anchor deliverymember.

FIG. 28A-28D are schematic views of an exemplary locking device. FIG.28A shows one configuration of a locking device with two tabs that areconfigured in series and bend inwards to push the tether against theinner wall of the locking device, thereby securing the locking device inplace and preventing it from sliding along the tether. FIG. 28B shows atether with inline male protrusions to facilitate locking of the tetherto the locking device. FIG. 28C shows another configuration of thelocking device where the two side walls are straight and at least onetab bends inwards against one side wall. FIG. 28D shows anotherconfiguration of the locking device with two tabs, each on each sidewall and the two tabs meet at the center of the locking device where itwill press against the tether to lock it in place.

FIGS. 29A and 29B are schematic views of an exemplary locking devicedelivery system, showing a handle, catheter and the supporting catheterfor the locking device.

FIG. 30 is a side elevational view showing a steerable sheath and handlecontroller.

FIG. 31 is a side view of the crimped prosthetic device, showing theeyelets of the prosthetic device are being captured by the slots on thelock housing structure.

FIG. 32A-32B are a perspective views of the lock housing structure andits perspective location within the valve catheter. FIG. 32A is aperspective view of an exemplary lock housing structure with four holesto house four tethers. FIG. 32B is a perspective view of the crimpedprosthetic device located within the delivery catheter, four tethers arelooped through the holes on the upper flared portion of the prostheticdevice, and the locking structure resides adjacent to the tip of theupper flared portion of the prosthetic device.

FIG. 33A-33B are views of the lock housing structure. FIG. 33A is aperspective view of the lock housing structure, showing five lumens, acentral slot for attachment to the main delivery system, four side slotsat the distal tip for engaging and pulling the eyelets of the prostheticdevice into the valve catheter. FIG. 33B is a cross-sectional view ofthe tip of the lock housing structure.

FIG. 34 is a perspective view of the valve catheter, showing the lockhousing catheter and a plurality of locks and lock catheters.

FIG. 35 is a cross-sectional view showing, positioned within a deliverycatheter, a lock housing structure, a stent positioned in a compresseddelivery position, and tether portions coupled to the stent.

FIG. 36 is a perspective view of a first linking structure and a secondlinking structure, the first linking structure binding the lock deliverycatheters and the second linking structures binding the lock supportingcatheter.

FIG. 37 is a perspective view of the valve catheter, showing a crimpedprosthetic valve, a plurality of tethers, the lock housing structure,and a plurality of locks and lock catheters.

FIG. 38 is a cross-sectional view of the delivery catheter, showing aplurality of lumens that are configured to guide the tether portionscoupled to the stent, and showing the stent positioned in the compresseddelivery position.

FIG. 39 is an exemplary schematic view of a plurality of anchorsinstalled at spaced installation points on the native mitral annulus.

FIG. 40 is a schematic partial cross-sectional view showing a pluralityof anchors implanted in the mitral annulus, and showing a tether portioncoupled to each anchor that extends through the delivery catheter.

FIG. 41 is a schematic partial cross-sectional view showing the deliverycatheter positioned inside the native mitral valve and a plurality oftethers coupled to respective anchors that extend from the deliverycatheter.

FIG. 42 is a schematic partial cross-sectional view showing the stentbeing deployed out of the catheter housing by advancing the lock housingstructure.

FIG. 43 is a schematic partial cross-sectional view showing the stentexpanded to an operative position (without the prosthetic leaflets forthe purpose of illustration) at the mitral annulus.

FIG. 44 is a schematic partial cross-sectional view showing an exemplaryposition of the deployed stent relative to the anchors prior to thestent being coupled to the plurality of anchors

FIGS. 45A-45B are schematic views of the stent being simultaneouslyoperatively coupled to a plurality of anchors using a locking devicedelivery catheter. FIG. 45A illustrates one exemplary aspect of fourlocking devices being delivered at four locations on top of the flareportion of the stent via four tethers.

FIG. 46 is a schematic view of a suture running circumferentiallythrough the stent structure at the level of the native mitral annulussuch that the suture can be used to selectively cinch the mitralannulus.

FIG. 47 is a schematic perspective view that shows the exemplaryocclusion of the atrial septum. In this aspect, a septal occluder isintroduced through the delivery catheter that extends through the atrialseptum hole. Subsequently, the delivery catheter is withdrawn throughthe atrial septum hole and the septal occluder is pulled towards theatrial septum until the hole is securely occluded by the septaloccluder.

FIGS. 48A-48B are pictures taken from in vitro test of the valveprototype. FIG. 48A was taken during valve opening with no pressure,wherein the flared portion of the device was positioned on top of themitral annulus and fixated by sutures and the ventricular portion (notshown) was inside the left ventricle. FIG. 48B was taken during valveclosure with a pressure about 120 mmHg. The prosthetic leaflets (P1, P2,and P3) can provide a surface for proper coaptation (i.e., visual acoaptation line) with the native leaflets.

FIG. 49A-49B are pictures taken from in vitro tests of the prostheticmitral valve prototype. FIG. 49A was taken during the release of thevalve from the valve catheter, while five anchors were pre-attached tothe mitral annulus. FIG. 49B was taken after the release of the valveprototype.

FIG. 50A-50B are pictures taken from in vitro tests of the prostheticmitral valve prototype. FIG. 50A was taken during the simultaneousrelease of the lock catheters. FIG. 50B was taken after release of thelock devices, and a pressure of 90 mmHg was applied, showing that thevalve is securely anchored to the mitral annulus.

FIGS. 51A-51D are computed tomography images of the heart valve leafletreplacement system after being surgically implanted in the native mitralposition of a porcine model. The images were taken during the systolicphase of a cardiac cycle. FIG. 51A shows the top view of the valve fromthe left atrium, showing all three prosthetic leaflets (P1, P2, and P3)coapting with the native anterior leaflet, the dark lines are thecoaptation lines and the bright lines represent the stent frame. FIG.51B is another view of the device, showing the prosthetic leaflet (P2)was coapting well with the native anterior leaflet (the arrow indicatesthe coaptation). FIG. 51C shows that the prosthetic leaflet (P1) wascoapting well with the native anterior leaflet (the arrow indicates thecoaptation). FIG. 51D shows the prosthetic leaflet (P3) is coapting wellwith the native anterior leaflet (the arrow indicates the coaptation).

FIG. 52 is echocardiogram of the implanted prosthesis inside the nativemitral valve during systole. The dynamic motion of the native leafletremains unperturbed after the implantation of the heart valvereplacement system. The leaflet can coapt well with the prostheticleaflets during systole.

FIGS. 53A-53F are a series of angiograms during the cardiac cycleshowing the heart valve replacement system after being surgicallyimplanted in the native mitral valve position of a porcine model. Fromthese images, it is shown that the prosthetic leaflets of the devicecoapt well with the anterior leaflet of the native mitral valve, wherethere is none to trace regurgitation during left ventricularcontraction. The data was obtained at 30-day follow up after theimplantation.

DETAILED DESCRIPTION

The present invention can be understood more readily by reference to thefollowing detailed description, examples, drawings, and claims, andtheir previous and following description. However, before the presentdevices, systems, and/or methods are disclosed and described, it is tobe understood that this invention is not limited to the specificdevices, systems, and/or methods disclosed unless otherwise specified,and, as such, can, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularaspects only and is not intended to be limiting.

The following description of the invention is provided as an enablingteaching of the invention in its best, currently known embodiment. Tothis end, those skilled in the relevant art will recognize andappreciate that many changes can be made to the various aspects of theinvention described herein, while still obtaining the beneficial resultsof the present invention. It will also be apparent that some of thedesired benefits of the present invention can be obtained by selectingsome of the features of the present invention without utilizing otherfeatures.

Accordingly, those who work in the art will recognize that manymodifications and adaptations to the present invention are possible andcan even be desirable in certain circumstances and are a part of thepresent invention. Thus, the following description is provided asillustrative of the principles of the present invention and not inlimitation thereof

For clarity, it will be appreciated that this disclosure will focus onthe treatment of functional mitral regurgitation, however it iscontemplated that the heart valve leaflet replacement system and theassociated methods can be used or otherwise configured to be used totreat other types of mitral regurgitation or to replace other diseasedvalves of the human heart, such as tricuspid valve, or could be used orotherwise configured to be used in other mammals suffering from valvedeficiencies as well.

As used throughout, the singular forms “a,” “an” and “the” includeplural referents unless the context clearly dictates otherwise. Thus,for example, reference to “a leaflet” can include two or more suchleaflets unless the context indicates otherwise.

Ranges can be expressed herein as from “about” one particular value,and/or to “about” another particular value. When such a range isexpressed, another aspect includes from the one particular value and/orto the other particular value. Similarly, when values are expressed asapproximations, by use of the antecedent “about,” it will be understoodthat the particular value forms another aspect. It will be furtherunderstood that the endpoints of each of the ranges are significant bothin relation to the other endpoint, and independently of the otherendpoint.

As used herein, the terms “optional” or “optionally” mean that thesubsequently described event or circumstance can or cannot occur, andthat the description includes instances where said event or circumstanceoccurs and instances where it does not.

The word “or” as used herein means any one member of a particular listand also includes any combination of members of that list. Further, oneshould note that conditional language, such as, among others, “can,”“could,” “might,” or “may,” unless specifically stated otherwise, orotherwise understood within the context as used, is generally intendedto convey that certain aspects include, while other aspects do notinclude, certain features, elements and/or steps. Thus, such conditionallanguage is not generally intended to imply that features, elementsand/or steps are in any way required for one or more particular aspectsor that one or more particular aspects necessarily include logic fordeciding, with or without user input or prompting, whether thesefeatures, elements and/or steps are included or are to be performed inany particular embodiment.

Disclosed are components that can be used to perform the disclosedmethods and systems. These and other components are disclosed herein,and it is understood that when combinations, subsets, interactions,groups, etc. of these components are disclosed that while specificreference of each various individual and collective combinations andpermutation of these cannot be explicitly disclosed, each isspecifically contemplated and described herein, for all methods andsystems. This applies to all aspects of this application including, butnot limited to, steps in disclosed methods. Thus, if there are a varietyof additional steps that can be performed it is understood that each ofthese additional steps can be performed with any specific embodiment orcombination of embodiments of the disclosed methods.

The present methods and systems can be understood more readily byreference to the following detailed description of preferred embodimentsand the examples included therein and to the figures and their previousand following description.

Described herein is a heart valve leaflet replacement system and amethod of securing a replacement prosthetic heart valve 12 to one of thenative valve annuli. In one aspect, it is contemplated that the heartvalve leaflet replacement system can be configured to secure aprosthetic mitral valve to the native mitral annulus. In a furtheraspect, the heart valve leaflet replacement system and the associatedmethods can be configured to alleviate mitral regurgitation during apatient's cardiac cycle and/or to help prevent further dilation of thenative mitral annulus. It should be noted that it is contemplated thatthe heart valve leaflet replacement system 11 described herein can beused to replace any diseased valve within the heart. For illustrationalpurposes, the description in this invention will be focused on themitral valve and the naming according to the mitral valve geometries.However, the designs described herein can be used in all other heartvalves accordingly.

Referring to FIG. 1, the mitral valve 1 is located on the left side ofthe heart, between the left atrium 9 and left ventricle 10 and hasanterior 1 and posterior 2 leaflets that are encompassed by the mitralannulus. In this aspect, the mitral annulus further has a fibrousportion 3, or fibrosa, which runs from the right trigone 6 a to the lefttrigone 6 b and is in continuity with a portion of the aortic valve andthe posterior muscular portion 4. Further, chordae tendineae 7 a, 7 boriginate from the respective major papillary muscles 8 a, 8 b of theleft ventricular wall and connect to the respective mitral leaflets.

In one aspect, the heart valve leaflet replacement system 11 cancomprise the replacement prosthetic mitral valve 12 and a transcatheterdelivery system. In this aspect, and referring to FIG. 2, disclosedherein an exemplary aspect of a heart valve leaflet replacement system11, showing the components and the fabricated prosthetic mitral valve12. In this aspect, the prosthetic mitral valve 12 can be configured tobe selectively compressed or otherwise constrained to a compressedposition and loaded onto the delivery catheter.

The prosthetic mitral valve 12 can comprise a crescent shaped stent 31,at least one mobile prosthetic leaflet 16, and at least one prongstructure 18 operatively coupling a portion of the prosthetic leaflet tothe lower ventricular portion of the stent 14.

In one aspect, the crescent shaped stent 31 of the replacementprosthetic mitral valve 12, as referring to FIGS. 2A-2B, can comprise anupper flared portion 13 and a lower ventricular portion 14. At least aportion of the upper flared portion 13 and/or a portion of the lowerventricular portion 14 can be formed to be self-expandable or balloonexpandable to the desired operative position. In this aspect, it iscontemplated that the stent 31 can be conventionally laser cut or woveninto a desired stent design that can be radially collapsible andexpandable. Thus, it is further contemplated that the stent can comprisea plurality of operatively linked components to form an expandablemeshed or non-meshed body that can be made of a metal, including but notlimited to, cobalt chromium, stainless steel; or a metal having inherentshape memory properties, including but not limited to, Nitinol.Optionally, it is contemplated that the stent can comprise a pluralityof vertical stiff structures that are connected by soft materials suchas biological tissue, synthetic materials such as polymers and the like.The stent can be configured to permit the natural dynamic motion of anyremaining native leaflet(s) to coapt with the prosthetic leaflet(s).

In one aspect, it is contemplated that, in the expanded configuration,the inner surface of the stent 31 can define a substantially circularcross-sectional profile. It is further contemplated that the stent 31can be configured to deform such that the inner surface of the stentdefines a non-circular cross-sectional profile, including but notlimited to, an elliptical cross-sectional profile or an asymmetriccross-sectional profile. As used herein, the term “asymmetriccross-sectional profile” includes any non-circular cross-sectionalshape.

In one aspect, as referring to FIG. 3, when implanted, it iscontemplated that the upper flared portion 13 of the stent 31 can beconfigured to be positioned on and/or above the native annulus. In thisaspect, the upper flared portion 13 of the stent 31 can be configured tofacilitate anchoring, fixating, and sealing of the stent, which canassist in preventing paravalvular leakage and dislodgement of the stentpost implantation. The mitral valve annulus is asymmetrical, which isillustrated in FIG. 3. The upper flared portion 13 of the prostheticmitral valve 12 will cover or overlay the posterior portion of themitral annulus, which is divided into three scallops: namely P1, P2 andP3. In one aspect, the upper flared portion 13 can span the twocommissures, i.e., the AC-anterior commissure and the PC-posteriorcommissure. In another aspect, the upper flared portion 13 can cover theentire circumference of the mitral valve when operatively positioned.

In one aspect, at least a portion of the lower ventricular portion 14can be positioned in the ventricular chamber of the heart and/or incontact with a portion of at least one native mitral leaflet.

FIG. 4 shows the computer generated stent 31 of the prosthetic mitralvalve 12 being overlaid with a computer model of the partial heart,comprising the aortic annulus 80, the partial left ventricle 10, thepapillary muscles 8, the left atrium 9, and the chordae tendineae 7.

Those skilled in the art will appreciate that the partial circumferenceframe 31 in this invention, as shown in FIG. 4, can help prevent leftventricular outflow tract 81 obstruction (LVOTO). One potentialadvantage of the partial circumference structure of the lowerventricular portion 14 of the stent is that the stent frame does notinterfere with the anterior mitral leaflet 1 when operativelypositioned. The native leaflet is not constrained by the stent and canmove freely, thereby reducing the risk of LVOTO. The lower ventricularportion 14 of the stent is configured to allow unperturbed motion of thenative anterior leaflet.

In one exemplary aspect, the lower ventricular portion 14 of the stentcan have a partial cylindrical or conical shape, and, optionally, canhave a height range of between about 0.5 to about 1.5 times the radiallength of the displaced diseased native leaflet(s). The lowerventricular portion 14 of the stent 31 can be configured to cover oroverlie only select portions of the native posterior annuluscircumference, and as a result of the expandable nature of the stent,can displace diseased native leaflet(s) out of the blood flow tract uponexpansion to an operative position. Since the lower ventricular portion14 can be configured to overlie select portions of the native annuluscircumference and not the entirety of the native annulus circumference,this “open” configuration allows for the dynamic motion of the remainingnative leaflet(s), e.g., the anterior mitral leaflet and for coaptationwith the prosthetic leaflet(s). In one aspect, the outer diameter of theupper flared portion can be between about 5 to 15 mm larger than theinner diameter of the lower ventricular portion when the stent isexpanded to the operative position.

In a further aspect, the lower ventricular portion 14 of the stent canextend radially from the anterior commissure 5 a to the posteriorcommissure 5 b, as exemplified in FIG. 3. In a further aspect, asexemplified in FIG. 3, the lower ventricular portion 14 of the stent canhave a “C”-shaped cross-section where one lateral edge 26 b lands at thecleft between the anterior leaflet and anterolateral commissure leafletand the other lateral edge 26 a lands at the cleft between the anteriorleaflet and the posteromedial commissure leaflet.

In one aspect, as shown in FIG. 5A, openings 24 defined in the upperflared portion 13 of the stent 31 can have a circular, square, diamond,triangle, or asymmetrical shapes. The area of the openings 24 of theupper flared portion 13 can have an area range from about 0.2 mm² to 2mm².

In one aspect, as shown in FIG. 5B, the angle between the upper flaredportion 13 and the lower ventricular portion 14 of the stent can varybetween 90 and 150 degrees, such that the stent frame can conform to thenative curvature of the left atrium.

In one aspect, as shown in FIGS. 6A-6E, it is contemplated that theheight of the lower ventricular portion 14 of the stent can vary alongthe covered annulus circumference. Optionally, the height of the lowerventricular portion 14 of the stent that covers the middle part 14 b ofthe posterior mitral leaflet can be substantially longer than, or thesame height as the lower ventricular portion 14 of the stent that coversthe two lateral parts of the posterior mitral leaflet 14 a, 14 c, asshown in FIG. 5A. It is contemplated that the lower ventricular portion14 of the stent that covers the two lateral parts of the posteriormitral leaflet 14 a, 14 c can be shorter in the axial direction suchthat it does not interfere with native anterior leaflet, chords, andleft ventricle when operatively positioned.

In one aspect, as shown in FIG. 8C, the lower ventricular portion 14 ofthe stent can be formed with at least one vertical member or elongatedstrut 85 that extends from at least one location on the upper flaredportion 13 of the stent 31. Optionally, this elongated strut 85 can be astraight or a curved segment extended axially, as exemplified in FIG.8D. In a further aspect, the elongated strut 85 can branch out to form asecondary strut to facilitate sewing of the linking skirt or leafletmaterials. It is contemplated that the elongated strut can be shaped asthat of the leaflet attachment edge, as exemplified in FIG. 8E.

As shown in FIGS. 7A-7C, the bottom 27 of the ventricular portion of thestent can be configured with features such as flanges, hooks, coils,clips, 32 that are configured to capture the native leaflets whenoperatively positioned. In this aspect, the device can be furtherfixated and anchored to the native valve. This capturing mechanism canalso further enable pannus formation that acts as sealing agent andprevents paravalvular leakage. In one aspect, as exemplified in FIG. 7A,upon deployment, at least three hook-like components 32 can extendradially from the stent strut and grab the native leaflets and chords.In one aspect, as exemplified in FIG. 7B, upon deployment, the hook-likecomponents 32 can extend only from the middle part of the stent 14 b. Inanother aspect, as exemplified in FIG. 7C, upon deployment, thehook-like components 32 can extend only from the lateral parts 14 a, 14c of the lower ventricular portion 14 of the stent 31.

In an expanded position, as exemplarily shown in FIGS. 5-9, the lowerventricular portion 14 of the stent 31 can have an outer diameterranging from about 20 mm to about 60 mm, and more preferably, from about30 mm to about 50 mm. In a particular exemplary aspect, and withoutlimitation, the lower ventricular portion 14 of the stent 31 can have anouter diameter of about 36 mm. However, it is contemplated that thelower ventricular portion 14 of the stent 31 can have any operativeouter diameter that permits proper positioning of the stent within theselected channel of the heart of the subject.

It is contemplated that the diameter of the stent 31, the spacingbetween parallel struts and/or adjacent openings within the mesh patternof the stent, and the mechanical properties of the stent can beselectively varied as necessary to achieve a desired position and/ordesired performance characteristics within the selected chamber of theheart of the subject. In exemplary aspects, the spacing between parallelstruts and/or the dimensions of adjacent openings within the meshpattern of the stent 31 can be non-uniform throughout the stent 31. Itis further contemplated that the stent 31 can be configured fordeformation to an elliptical shape. It is still further contemplatedthat the mesh configuration of the stent 31 can provide sufficientstructural integrity to prevent collapse of the stent upon exposure tocompressive loading during valve closure, including but not limited to,mitral valve closure. In addition, the stent 31 can be configured toaccommodate and tolerate sufficient radial expansion force to permitsecure positioning of the stent on the mitral annulus within the heartof the subject.

In one aspect, as exemplified in FIG. 9, it is contemplated that thelower ventricular portion 14 of the stent 31 can extendcircumferentially less than 360 degrees, while the coupled upper flaredportion 13 can be formed to extend circumferentially about 360 degrees.

In one aspect, the replacement prosthetic mitral valve 12, as shown inFIG. 2, can comprise a skirt 28 that can be coupled to at least aportion of the inner and outer surfaces of the stent. In one exemplaryaspect, it is contemplated that the skirt 28 can be sewn to at least aportion of the inner and outer surfaces of the stent with non-absorbablesutures. In an exemplary aspect, the skirt 28 can be formed ofbiocompatible materials, for example but not limited to, biocompatiblefabric, bovine, or porcine pericardium, and the like.

In one aspect, the at least one prosthetic leaflet 16 can be mounted onthe inner surface of the stent. In one aspect, the at least oneprosthetic leaflet 16 can be mounted on the inner surface of the lowerventricular portion 14 of the stent 31. It is contemplated that theprosthetic mitral valve 12 can comprise a plurality of prostheticleaflets 16, in which all of the leaflets can have the same shape or inwhich one or more of the plurality of leaflets can have a differentshape. In various aspects, each leaflet can comprise a free edge 17, twocommissure attachment regions 19, an attachment edge 18, and respectivecoaptation 21 and belly regions 20.

In one aspect, the at least one prosthetic leaflet 16 can be configuredto be mobile throughout the cardiac cycle such that the prostheticleaflet 16 can coapt with at least one native leaflet during valveclosure to prevent the regurgitation of blood through the valve. In oneaspect, the prosthetic leaflets 16 can be flexible and mobile enough tocontact with the native leaflet 1 without damaging the native leaflet,and can open fully during valve opening such that it does not to perturbnormal blood flow through the valve or induce stenosis.

In one aspect, as exemplified in FIG. 10A, each prosthetic leaflet 16can have additional extension tissues 22 on the free edge 17 that areconfigured to increase the coaptation zone between the prostheticleaflets and the native anterior leaflet. In this aspect, it iscontemplated that a plurality of prong structures 23 can be configuredto be coupled to the coaptation enhancing extension tissues 22. Theadditional tissue 22 on the free edge 17 of each prosthetic leaflet 16can be between about 1 to about 10 mm. In this aspect, the prongstructures can be configured to shape the prosthetic leaflets into anoptimal coaptation surface for the native anterior mitral leaflet whenpressurized to ensure optimal coaptation and prevent prolapse and theleakage of blood through the valve.

In one aspect, as exemplified in FIGS. 10B and 10C, the prosthetic valvereplacement can comprise three prosthetic leaflets 16: a middle leaflet16 b and two side leaflets 16 a, 16 c. The middle prosthetic leaflet 16b can have a plurality of prong structures 23 and the two sideprosthetic leaflets 16 a, 16 c can be without prong structures 23. Inanother aspect, the height of the commissure attachment regions 19 ofthe prosthetic leaflets 16 can be the same or different. In a furtheroptional aspect, as shown in FIG. 10C, the commissure attachment regions19 of the two side prosthetic leaflets 16 a, 16 c can be shortened atthe two lateral edges 26 a, 26 b of the lower ventricular portion 14 ofthe stent 31.

In one embodiment of the replacement prosthetic heart valve shown inFIG. 2, the two commissure leaflets 16 a, 16 c can span about 30°-60° ofthe stent circumference. In one exemplary aspect, the commissure leaflet16 a,c shown in FIG. 10A can have a maximum width of 15.0 to 30.0 mm andheight of 10.0 to 20.0 mm, where the extended free edge portion is about1.0 to 6.0 mm higher than the tip of the leaflet-stent attachmentsillustrated in FIGS. 15 and 16. In this aspect, the extended free edgecan ensure sufficient coaptation between the prosthetic commissureleaflets 16 a, 16 c and the native anterior mitral leaflet at A1 and A3regions referring to FIG. 3 as well as the middle prosthetic leaflet 16b while keeping the overall stent height low to prevent deviceinterference with the surrounding native structures, i.e. the papillarymuscles and myocardium, when operatively positioned. Further in thisaspect, the prong structure can have a length of 5.0 to 15.0 mm and actto stabilize the extended free edge and aid in proper coaptation betweenthe sides of native anterior mitral leaflet and prosthetic commissureleaflets with a coaptation height of about 2.0 to 7.0 mm. The tip of theprong structure 23 can be configured to be at an angle of about 20° tofacilitate attachment to the similarly angled stent strut and the prongstent attachment points shown in FIGS. 15 and 16. Referring to FIG. 10A, the middle prosthetic leaflet 16 b can span about 60°-120° of thestent circumference. Preferentially, the middle leaflet 16 b can beconfigured to span a larger circumference of the stent than the two sidecommissure leaflets 16 a, 16 c such that the prosthetic leaflets canbetter coapt with the native anterior mitral leaflet at the A2 regionduring valve closure. In one exemplary aspect, the middle prostheticleaflet 16 b can have a maximum width of 20.0 to 35.0 mm and height of10.0 to 20.0 mm, where the extended free edge portion is about 1.0 to7.0 mm higher than the tip of the leaflet-stent attachment pointsillustrated in FIGS. 15 and 16. In this aspect, the extended free edgecan ensure sufficient coaptation between the middle prosthetic leaflet16 b and the adjacent prosthetic commissure leaflets 16 a,c as well asthe native anterior mitral leaflet at A2 with a coaptation height ofabout 4.0 to 7.0 mm while keeping the overall stent height low. Furtherin this aspect, the middle prosthetic leaflet 16 b can be configured tohave two prong structures extending from the extended free edge 22 witha length of 5.0 to 15.0 mm that can act to stabilize the extended freeedge and aid in proper coaptation between the middle prosthetic leaflet16 b and native mitral anterior leaflet.

In one aspect, the at least one prosthetic leaflet 16 can be mounted onthe inner surface of the upper flare portion 13 of the stent 31.Optionally, selective portions of the prosthetic leaflet 16 can bemounted on the outer surface of the stent 31, for example, theprosthetic leaflets can be wrapped around the sides of the stent 31 toact as a cushion between the stent 31 and native tissue when operativelypositioned.

Referring to FIG. 11, the plurality of prosthetic leaflets 16 can beconfigured without prong structures 23 extending from the leaflet freeedge 17. In one aspect, shown in FIGS. 11A and 11B, the prosthetic valvereplacement can be configured with two identical leaflets. In anotheraspect shown in FIGS. 11C and 11D the prosthetic valve can be configuredwith three identical leaflets 16. Optionally, the commissure sideleaflets 16 a, 16 c can be differ in shape to the middle leaflet 16 b asshown in FIGS. 11E and 11F. Further in this aspect, the plurality ofprosthetic leaflets can be configured to vary in the number of leaflets,size, height, and length, as shown in FIGS. 11G and 11H, to permitproper coaptation and opening.

Referring to FIG. 12, in one aspect, the prong structures 23 can becoupled to the leaflet free edge 17. In another exemplary aspect, theprong structures 23 can couple to the leaflet belly 20, or optionally tothe extended free edge zone 22. It is contemplated that the prongstructures 23 can be configured with a differing material to theprosthetic leaflet 16, for instance, but not limited to, biocompatiblefabric, suture, or tissue, and can be attached to the prosthetic leaflet16 in a number of ways, for instance by adhesive or suturing, to variousregions on the prosthetic leaflet 16.

Referring to FIG. 13, in one aspect of the prosthetic valve replacement,the plurality of prosthetic leaflets 16 can be attached to the innersurface of the ventricular portion of the stent 14 along the leafletattachment edges 18 as well as at the attachment tabs on the prongstructures.

In another aspect, referring to FIG. 14, the plurality of prostheticleaflets 16 can be configured without prong structures 23 and can beattached to the inner surface of the ventricular portion of the stent 14along the leaflet attachment edges 18 only. Optionally, the commissureleaflets 16 a, 16 c can be shorter on the sides away from the centerleaflet 16 b corresponding to one aspect of the ventricular portion ofthe stent 14 where it is shorter on the sides.

Optionally, the at least one prosthetic leaflet 16 can have a shapesimilar to the native diseased valve the prosthetic valve 12 is intendedto replace, or a different shape from those illustrated in FIG. 10 toFIG. 12, including, but not limited to, a square, rectangular,triangular, oval, circle, or other asymmetric shape.

In one exemplary aspect, the prosthetic leaflets can be configured toattach to the stent at a juncture defined by the two-dimensional andthree dimensional leaflet-stent attachment curves shown in FIGS. 15-16,where the solid dots indicate the leaflet edge 18 attachment points, andthe open triangles indicate the prong structure 23 attachments to thestent. This specific leaflet and prong stent attachment design and itsvariations (+/−25% derivation from the illustrated design curves) areoptimized for optimal leaflet coaptation and well as leaflet stressreduction during the cardiac cycle while having a large effectiveorifice area without hitting the stent during valve opening. This designcan be scaled, or proportionally adjusted, or un-proportionally adjustedfor different sizes of the valve, provided these structures of theleaflet and prongs are used for the purpose of maintaining propercoaptation and reducing leaflet stress and increasing valve durability.

In one aspect, a means for guiding and anchoring the prosthetic valve 12to the native annulus can comprise a plurality of fixation memberscoupled to flexible and elongated components. In one aspect, thefixation members can be anchors, hooks, or barbs that fixate into theannular tissues. The fixation members, for example, the anchor 30 can besequentially delivered and implanted at the desired locations via asteerable catheter. In a further aspect, it is contemplated that amethod of implanting anchors 30 can be implemented prior to the deliveryof the prosthetic mitral valve 12. In another aspect, a plurality ofanchors 30 can be configured to help prevent leakage of blood betweenthe operatively positioned prosthetic valve 12 and the native mitralannulus. In another aspect, a plurality of anchors 30 can be configuredto facilitate cinching of the diseased annulus in the circumferentialdirection to reduce the annular dimensions.

In another aspect, the plurality of anchors 30 can be directly attachedto the stent. In this aspect, it is contemplated that the prostheticvalve 12 can be deployed simultaneously with the anchors 30, and theanchors 30 can be selectively configured to engage the native annulusonce the prosthetic valve 12 is in the operative position to fixate thedevice on the native annulus.

In one aspect, as exemplified in FIGS. 17-21, each anchor 30 cancomprise a distal portion 39, a proximal portion 40, and a tetherportion 44. It is further contemplated that the distal portion 39 ofeach anchor 30 can be configured to implant into the native annulustissue and to resist separation after implantation. In an exemplaryaspect, the distal portion of each anchor 39 can have, but is notlimited to, a spiral shape, a coil shape, a pronged shape, a screwshape, and a barbed hook shape. The anchors 30 can be formed of, but arenot limited to, Nitinol, stainless steel, cobalt chromium, polymer, andthe like.

As one skilled in the art will appreciate, the anchors in this inventionare specially configured to safely secure the prosthetic mitral valve 12on the muscular annular section of the mitral valve. The anchor 30, asexemplified in FIG. 17, is configured to withstand the total forceexerted to the prosthetic leaflet, without being pulled off the muscularportion of the annulus. Table 1 of FIG. 17 shows that the total forceexerted to the prosthetic leaflet can be estimated by calculating thetotal area of prosthetic leaflet surface and the ventricular pressure.Table 1 displays two exemplary prosthetic valve sizes and the calculatedforces exerted on the prosthetic leaflet. In one aspect, for an averagesize 29 mm diameter valve, assuming 140 mmHg of ventricular pressure, atotal force of 12.33 N is required to secure the prosthetic mitral valve12 in the native valve. Therefore, it is contemplated that the number ofanchors to be used should be able to hold at least a total force of12.33 N.

It is contemplated that each anchor configuration in this invention, asexemplified in FIGS. 17-24, can withstand at least 3 N, at least 4 N, orat least 5 N. In one aspect, one anchor can be placed at the rightcommissure (right trigone region of the mitral valve) and the otheranchor can be placed at the left commissure (left trigone region of themitral valve). It is contemplated that the height of the proximalportion 40 of the anchor 30 can be between about 1 and about 3 mm, andthe length of the distal portion 39 of the anchor can be between about 3and about 6 mm. In an exemplary aspect, as shown in FIGS. 17 to 21, thedistal portion 39 can have a coiled shape with between about 3 to 6coils. In this aspect, it is contemplated that the coiled distal portion39 can have a wire diameter of 0.3 to 1 mm, and the formed outerdiameter of the coiled distal portion 39 can be from about 2 to about 5mm.

In one aspect, the tip 43 of the distal portion 39 of the anchor 30, asexemplified in FIG. 18, can comprise a tip that is shaped and configuredto facilitate easy penetration into the annular tissue. In one exemplaryaspect, the tip 43 of the distal portion 39 of the anchor 30 is curvedto the same pitch as the distal portion 39 of the anchor 30. In anotherexemplary aspect, the tip 43 of the distal portion 39 of the anchor 30can be straight. Optionally, the tip 43 of the distal portion 39 of theanchor 30 can have an arc length of from about 1 mm to 3 mm.

In another aspect, as shown in FIG. 18, the proximal portion 40 of theanchor 30 can define a slot 47 that is configured for attachment of atether. It is contemplated that the tether 44 can be looped through theslot 47 on the proximal portion 40 of the anchor 30. Optionally, theproximal portion 40 of the anchor 30 can also define two L-shaped slots72 that are configured to receive two pins 50 inside the anchor deliverycatheter tip 49, as shown in FIG. 19A-19C. In this aspect, it iscontemplated that the anchor 30 could be operatively implanted byrotating the anchor delivery catheter 48 in a first rotative direction.Further in this exemplary aspect and as one skilled in the art willappreciate, the anchor 30 can be subsequently separated from the anchordelivery catheter tip 49 by rotating the anchor delivery catheter 48 ina second rotative direction that is opposite to the first rotativedirection to remove the pins 50 from the slots on the proximal portionof the anchor 30.

As shown in FIGS. 20-21, it is contemplated that the means for lockingthe stent 31 to the anchors 30 can comprise at least one lockingstructure 45, including but not limited to, ridge engaging teeth, barbs,zip ties, pliable barb or key element, a cone shape, a square shape, anarrow shape, a circular shape, a triangular shape, a dome shape, and thelike. It is contemplated that the locking structures 45 can beconfigured to allow passage of a portion of the upper flared portion 13of the stent 31 down the tether portion 44 towards the left ventricle10, and to resist the subsequent movement of the upper flared portion 13of the stent 31 in the opposite direction. In another aspect, it iscontemplated that the locking structures 45 can be configured in seriesalong the tether portion 44 to allow for adjustment of the distancebetween the stent 31 and the anchor 30, and allow the stent 31 to beoperatively locked even when there is a misalignment between the stent31 and anchors 30. In an exemplary aspect, it is contemplated that theone or more locking structures 45 can be formed of, but are not limitedto, polymers, polytetrafluoroethylene (PTFE), metallic materials, or acombination of these materials.

In another aspect, as shown in FIGS. 22 to 24, the distal portion 39 ofthe anchor can comprise a plurality of barbed segments that are curvedat an acute angle with respect to the longitudinal axis of the anchor.In an exemplary aspect, the acute angle can be between about 45 andabout 90 degrees. In a further aspect, the barbed segments can have acurved cross-sectional shape. In one aspect, the barbed segments canhave a length of between about 3 and 5 mm.

As shown in FIG. 22, it is contemplated that the proximal portion 40 ofthe anchor can comprise solid rod structures.

As shown in FIGS. 23 and 24, the proximal portion 40 of the anchor candefine one or more openings to allow for tissue ingrowth andneovascularization after implantation, to help the binding of theimplanted anchor to the native tissue permanently, and thereby toprevent disengagement and dislodgment of the anchor. In this aspect, theanchors 30 can be configured to help the upper flared portion 13 of thestent 31 stay in a locked position for the entirety of its use. It iscontemplated that the anchor 30 can be delivered in one or more steps tothe native mitral annulus using a dilator coupled with a guide-wire andanchor delivery catheter. In this aspect, it is contemplated that theanchors 30 can be advanced into the formed hole in the mitral annulus,can be deployed by removing from the anchor from the anchor deliverycatheter, and finally can be locked in position by pulling back on thetether portion 44.

Optionally, and referring now to FIGS. 25 to 26, the proximal portion 40of the anchor can comprise a threaded surface 46 that is configured tobe complementarily received within a threaded portion of an anchordelivery catheter 48. In this aspect, as exemplified in FIG. 27, it iscontemplated that the coiled distal portion 39 of the anchor 30 could beimplanted by rotating the anchor delivery catheter 48 in a firstrotative direction. As one skilled in the art will appreciate, theanchor 30 can be subsequently separated from the threaded portion 46 ofthe anchor delivery catheter 48 by rotating the anchor delivery catheterin a second rotative direction that is opposite to the first rotativedirection to unscrew the threaded surface of the proximal portion 40 ofthe anchor from the threaded portion of the anchor delivery catheter 48.

It is further contemplated that the elongated tether portion 44 can beconfigured to help position and secure the prosthetic mitral valve 12 tothe implanted anchors 30. Optionally, it is contemplated that the tetherportion 44 can be coupled to the proximal portion 40 of the anchor 30and can be long enough to extend outside the patient's body, where it isconnected to the lock delivery system. In another aspect, as exemplifiedin FIG. 28B, a portion of the tether adjacent to the proximal portion 40of the anchor can have at least one male protrusion that is configuredto facilitate locking of the tether within the locking device andthereby locking the stent 31 in the operative position. In one aspect,each male protrusion can be a formed by a knot in the tether material,or optionally by adding additional material to form a male protrusion.The tether portion 44 can be formed of, but not limited to, polymers,polytetrafluoroethylene (PTFE), metallic materials, or a combination ofthese materials.

Optionally, the tether 44 can comprise a suture-like section and ametallic section. In this aspect, it is contemplated that thesuture-like section can be pre-attached to the proximal portion 40 ofthe anchor and the metallic section can be pre-attached to thesuture-like section. The metallic section can be removed from the bodyfollowing the implantation of the prosthetic mitral valve 12 while thesuture-like section can remain in the body to secure the prostheticmitral valve 12 to the mitral annulus.

In a further aspect, the method of delivering the prosthetic mitralvalve 12 can be based on optional delivery access approaches. In oneexemplary aspect and as described in more detail below, the method canentail a trans-septal access approach. In this aspect, an opening can becreated in the internal jugular vein for the subsequent minimallyinvasive delivery of portions of the heart valve leaflet replacementsystem through the superior vena cava which flows into the right atriumof the heart. In this exemplary aspect, the delivery path crosses theatrial septum of the heart, and once achieved, the prosthetic mitralvalve 12 of the heart valve leaflet replacement system can operativelyaccess the left atrium 9, the native mitral valve, and the leftventricle 10.

In this aspect, it is contemplated that the delivery path to the nativemitral valve can be accessed trans-septally via a formed opening in thefemoral vein, or the delivery path to the native mitral valve can bedone trans-apically. In one aspect, it is contemplated that a maindelivery catheter 62 can be placed along the delivery path to allow allof the delivery components of the heart valve leaflet replacement system11 needed for the implant procedure to enter the left atrium 9 withoutcomplications.

In one aspect, a delivery catheter 62 can be configured for the deliveryof the prosthetic mitral valve 12 to the previously implanted anchors30. Prior to the deployment of the prosthetic mitral valve 12, thetether portions 44 extending from each of the anchors 30 can be passedthrough the openings 24 of the upper flared portion 13 of the prostheticmitral valve 12.

In one aspect, as exemplified in FIG. 30, a delivery catheter 62 cancomprise a sheath that is attached to a selectively deflectable tip 65that is configured to be selectively oriented. The delivery catheter 62can further comprise a handle 64 that houses a guidewire 63 andconventional means for steering the deflectable tip 65.

Referring to FIG. 44, a plurality of anchors 30 can be sequentiallyimplanted in the native mitral annulus. Subsequently, the prostheticvalve 12 can be delivered and positioned such that the upper flaredportion 13 of the stent 31 can be in close proximity to the anchors 30.Optionally, it is contemplated that a method of retrieving theprosthetic valve 12 back into the delivery catheter 62 can beimplemented to ensure the optimal delivery and positioning of theprosthetic valve replacement 12 inside the native mitral annulus.

In one aspect, it is contemplated that a two-step crimping procedure canbe implemented to prepare the crescent shaped stent 31 into thecompressed configuration within the valve catheter. In the first step,the two ends 26 a, 26 b of the crescent shaped stent can be joinedtogether to form a full cylindrical shape by using a locking mechanismincorporated into the stent structure. The two ends 26 a, 26 b of thestent structure can have locking components, including but not limitedto, hooks, teeth, and slots. In the second step, one end of theprosthetic valve can be squeezed and inserted into a series of conesand/or tubes until it reaches the desired crimping profile, then theprosthetic valve can be loaded into the delivery catheter 62. Theprosthetic mitral valve 12 can be compressed using a transcatheter valvecrimper.

The tether portion 44, extending from the proximal portion 40 of theanchors 30 and exiting the body, can pass through the openings 24 of theupper flared portion 13 prior to crimping of the prosthetic mitral valve12. Then, the tethers 44 can be squeezed and crimped together with theprosthetic mitral valve 12. In this exemplary aspect and as one skilledin the art will appreciate, the tether portions 44 reside between thestent and the inner wall of the delivery catheter 75 can be twisted andtangled, thus, making it difficult to introduce the prosthetic valve tothe native position. In order to smoothly slide the prosthetic valve 12along the delivery catheter 62, it is contemplated that each tetherportion 44 can be housed within a tubular catheter while being crimpedwith the prosthetic mitral valve 12. The tubular catheter can be made ofstainless steel, Nitinol, Nylon, polyester, PTFE, EBAX (nylonco-polymer), PET, PUR, EVA, or custom blend materials and the like. Itis further contemplated that the tubular catheter can be dimensioned tofit within the openings 24 of the upper flared portion 13 of theprosthetic mitral valve 12. The tubular catheter can extend to thedistal end of the tethers 44 connected to the anchors 30 in the nativevalve to prevent the tangling of the tethers within the main deliverysheath 62. In operation, once the prosthetic mitral valve 12 ispositioned at the tip 65 of the deflectable delivery sheath in thenative left atrium 9, the tubular catheter can be removed prior to therelease of the prosthetic mitral valve 12.

The method of locking the stent 31 to the native annulus can be achievedusing locking devices 70, as exemplified in FIG. 28, which can beattached to the tether portion 44. It is contemplated that the lockingdevices 70 can be delivered in individual succession or simultaneouslyafter deploying the prosthetic mitral valve 12. It should be appreciatedthat by securing the prosthetic valve 12 using the locking devices 70,the annulus of the diseased valve can be reshaped to the shape of theprosthetic device 12 by pulling a plurality of tethers coupled to theanchors 30 which are already embedded in the native tissues. In oneexample for a dilated annulus, the distances between the anchors 30 onthe annulus 4 will be larger than the distances between the hollowstructures 24 on the upper flared portion 13 of the stent 31. Thus,pulling the tethers 44 while delivering the locking devices can draw orreduce the diameter of the dilated and diseased annulus. In this aspect,this system of placing a locking device at any preferred location alongthe tether allow marginal errors for placement of the anchors 30 on theannulus

A lock housing structure 51, as exemplified in FIG. 32, can besubsequently loaded within the delivery sheath 62. In one aspect, thelock housing structure 51 can be configured to operatively house thetether(s) 44 and the lock delivering catheter(s) 57. In one aspect, thelock housing structure 51 can define a proximal portion 53 and a distalportion 52, where the distal portion 52 contains a plurality of lumens54 for the tethers to pass through, as shown in FIG. 32A. The distalportion 52 is positioned adjacent to the upper flared portion 13 of thestent 31. Optionally, only a portion of the distal tip of the lockhousing structure 51 can be configured to define the plurality of lumens54 for the tethers 44 to pass through.

In another aspect, the lock housing structure catheter 51 can have aplurality of lumens 54 having a shape and configuration as illustratedin FIGS. 33A-33B. In this aspect, the dimensions of these lumens areconfigured to house the entire locking device delivery catheter 57. Itis contemplated that two or more locking devices 70 could be deliveredsimultaneously upon the release of the prosthetic valve while rapidpacing is in place. Hence, the multiple lumen 54 of the lock housingstructure 51 allow for two or more locking devices to be deliveredrapidly.

Referring to FIG. 33, it is contemplated that the outer wall of thedistal portion 52 of the lock housing structure 51 has two or morerecesses 76 for insertion of two or more eyelets 77 of the stent. Inthis aspect, two or more eyelets 77 of the stent, as shown in FIG. 34,can be used to load the stent into the stent sheath 75. The crimpeddevice 74, as exemplified in FIG. 31, can be subsequently loaded withinthe stent sheath 75. A cross sectional view of the lock housingstructure 51, crimped stent 74, and tethers 44 is illustrated in FIG.35.

It is contemplated that the locking device 70 can comprise a structurewith a passage that allows at least one tether 44 to pass through. In afurther aspect, the locking device 70 can be manipulated to be lockedwithin a designated portion of the tether 44. In one aspect, the lockingdevice 70 can be but not limited to a tubular structure, as exemplifiedin FIG. 28, which can clamp on to at least one of the tethers 44 usingone or more tabs 59 extending radially inwards from the one side wall ofthe tubular structure and forming a tight contact against the oppositeside of the tubular structure. The tethers 44 can have inline maleprotrusions that are configured to increase friction and axialresistance to prevent tether slippage. In this aspect, the tubularlocking device 70 can be delivered and released using a locking deliverysystem.

In one aspect, the locking device 70 can be configured as a non-circularstructure with passage for at least one tether to pass through. In anexemplary locking device, as exemplified in FIG. 28C, at least one tabis cut out and bent inwards from at least one flat side of the lockingdevice. In this aspect, a tether 44 can form a tight contact against theside wall of the locking device. In a further aspect of this exemplarylocking device, the edge of the tab 59 can be edged or electro-polishedso that it will not cut into the tether.

In an additional aspect, the locking device 70 can be configured withtwo tabs 59, as exemplified in FIG. 28D, one on each side wall. The twotabs 59 are configured to bend inwards and meet at the center of thelocking device 70. In this aspect, both tabs can press against thetether to allow tighter contact between the tether and the lockingdevice.

In one aspect, as shown in FIG. 34, the lock delivery componentscomprise a plurality of locks 70, a lock delivery catheter 57, a locksupporting tube 56, and a lock delivery catheter handle 58. In oneaspect, the inner diameter of the locking device 70 can be slightlylarger than the outer diameter of the supporting catheter 56, withlittle to no sliding between the two components. The lock supportingcatheter 56 can comprise stiff 82 and flexible 83 portions. In thisaspect, the stiff portion, as exemplified in FIG. 29, can be configuredto open one or more tabs 59, i.e., push the tabs towards the wall of thelocking device, to thereby allow the tether 44 to pass through therebyfacilitating sliding of the locking device 70 along the tether 44. Inthis aspect, it will be appreciated that the flexible portion 83 of thelock supporting catheter 56 is configured to allow the catheter to flexand bend easily which will facilitate delivery of the locking device 70at different locations around the annulus. In this aspect, the lockingdelivery catheter 58 is a flexible catheter, which can be conventionallyoperated to push the locking device 70 away from the stiff 82 portion ofthe locking supporting catheter 56 so that it can release the tabs 59and couple to the tether 44 within the tubular structure of the lockingdevice 70 to effectively lock the locking device into place along thetether 44. In a further aspect, the locking deliver catheter 58 can betapered to a smaller diameter at the distal portion, adjacent to thelocking devices 70, to facilitate the pushing and delivering of thelocking devices 70.

In another aspect, the lock support catheter 56 can be configured as asingle portion made of a single material. In this aspect, the locksupport catheter 56 can be configured to be flexible, suchconfigurations include but not limited to laser cutting a zig-zagpattern or a spiral cut through the wall.

In an optional aspect, the delivery system can be configured such thatall locks 70 are released simultaneously immediately after the releaseof the stent. In this aspect, it is contemplated that, as exemplified inFIG. 36, the locks 70 can be coupled together by a linkage mechanism,which can be a solid linking structure 78 with holes defined thereinthat is configured to secure and lock a plurality of the lock supportingcatheters 56 in place. In this aspect, since the locks 70 also need tobe released simultaneously, a second linkage structure 79 can also beconfigured to secure a plurality of lock delivery catheters 57. It iscontemplated that both first and second linkage structures 78,79 can beconfigured to couple to the catheter system handle to enablesimultaneous release with the stent.

Operatively, to help prevent the tangling of the tethers 44 with thestent 31 of the prosthetic mitral valve 12, the distal portion of thedelivery sheath 62 can be configured to have at least four slots 55formed within the delivery catheter sheath 62 that are each sized toaccept a tether portion 44. FIG. 38 is a cross-sectional view of thedelivery catheter 62 in which the stent of the prosthetic valve 12 ishoused in the compressed position within a central lumen of the deliverysheath 62, and the slots 55 are formed in the wall thickness of thedelivery sheath 62. It is further contemplated that the formed slots 55can be evenly spaced or asymmetrically spaced inside the sheath to alignwith the housed stent 12.

Referring to FIG. 47, the prosthetic mitral valve 12 can be delivered tothe native mitral valve from the internal jugular vein, via the superiorvena cava 66 and across the atrial septum 68. In this exemplary method,a guidewire 63 can be inserted into the body through an incision in theinternal jugular vein. The guidewire 63 is advanced along the internaljugular vein to the right atrium of the heart via the inferior vena cava67.

Subsequently, the guidewire 63 is directed into the left atrium 9 bycrossing the septal wall 68 and is then brought through the nativemitral valve and positioned in the left ventricle 10. In this method, inan optional aspect, one or more dilators can then be advanced along theguidewire 63 to open the trans-septal perforation to allow the deliverycatheter 62 to cross the septum 63.

Once across the atrial septum 68, the tip 65 of the steerable cathetercan be bent towards the first desired location within the mitral annulusfor deploying the anchors 30, and the first anchor 30 is implanted atthe first desired position, as exemplified in FIG. 39. In this aspect,it is preferred that the first desired location be located in either theleft 6 b or right trigone 6 a regions. In one aspect, the preferredfirst desired location embodiment is in the left trigone 6 b. Anchors 30are sequentially delivered and implanted via the steerable catheter 69until all of the desired anchors 30 are implanted therein the desiredlocations within the mitral annulus. When each anchor 30 is implanted,the anchor delivery catheter 48 is removed and the tether portion 44 isretained within the steerable delivery catheter 69, as exemplified inFIG. 40.

During the subsequent prosthetic valve replacement deployment procedure,the tether portions 44 can be slightly tensioned to guide respectiveanchor pusher catheters 51 as they are advanced towards the prostheticvalve 12 to push the prosthetic valve 12 towards the anchors 30. FIG. 41schematically illustrates positioning the prosthetic valve 12 at thenative mitral valve. It is also contemplated that the prosthetic valve12 deployment procedure can occur while rapid pacing is in place. In oneexemplary view, shown in FIG. 42, the stent delivery sheath 75 can beselectively pushed outside the steerable tip 65 when the steerable tipof the delivery catheter is positioned next to the tip of the posteriorleaflet or deep into the left ventricle.

It is contemplated that the prosthetic mitral valve 12 can be deliveredby pushing the lock housing structure catheter 51. Once the stent of thereplacement prosthetic mitral valve 12 is fully ejected from thedelivery sheath, the upper flared portion 13 of the prosthetic mitralvalve 12 can operatively situate on top of the native annulus, asillustrated from different views in FIGS. 43 and 44.

In one aspect, it is contemplated that a two-step deployment procedurecan be implemented to release the crescent shaped prosthetic mitralvalve 12 into the normal functional configuration. In the first step,the prosthetic mitral valve 12 can be deployed into the left ventricle10 at the level of the native mitral annulus, during which theprosthetic mitral valve 12 can maintain a full cylindrical shape withthe locking mechanism of the two ends 26 a, 26 b still in place. Theprosthetic mitral valve 12 can be oriented in a way that the markers onthe stent structure can correspond to the two trigones 6 a, 6 b of thenative mitral annulus. In the second step, the locking mechanism of thetwo ends 26 a, 26 b of the stent can be released and the prostheticmitral valve 12 can be deployed into the designed semi- cylindricalshape to replace the native posterior mitral leaflet 2.

Subsequently, the stent of the prosthetic valve 12 can be locked inposition relative to the native annulus by locking the anchors 30 toanchor openings of the upper flared portion 13 of the stent. Bytensioning the anchor tethers 44 and locking the stent 31 in place bythe anchors, the native annulus can be reshaped to the stent shape. Itis contemplated that the means for locking the stent to the anchor 30can provide flexibility so that the stent 31 of the prosthetic valve 12can be locked in place at the annulus even when the anchors are deployedin a non-optimal configuration, i.e., when the anchors 30 are unevenlyspaced or out of plane from each other.

In a further aspect, the stent 31 of the prosthetic valve 12 can belocked to the anchors simultaneously using the anchor delivery members.Pulling the tethers while slightly pushing the anchor delivery memberscan further reduce the annulus and allow the annulus to be cinchedradially after locking the stent 31 in place.

In one aspect, the method of fixating the heart valve replacement systemcan be achieved by deploying the prosthetic valve 12 within a previouslyimplanted docking station, consisting of a stent or structure meant tohold the heart valve replacement system in place, an annuloplasty bandor ring, or a ventricular band or ring. It is contemplated that a heartvalve leaflet replacement system that can be expanded to a largerdiameter than the previously implanted device, can be deployed withinthe previously implanted device and provide enough frictional force tofixate the heart valve leaflet replacement system 12 in the operativeposition without the need for additional anchors or sutures.

In one aspect, an optional means for cinching the mitral annuluscircumferentially is shown in FIG. 46. This means for cinching canentail a cinching tether 61 that extends circumferentially along themitral annulus. In this aspect, an additional cinching tether 61 can bepre-attached to the upper flared portion 13 of the stent 31. Optionally,an additional cinching tether 61 can be pre-attached to the anchor(s)30. Operationally, once the stent 31 of the prosthetic mitral valve 12is locked to the anchors 30, the cinching procedure can be carried out.In one embodiment, the locking means of this cinching tether 61 can beof similar design to the means for locking the stent to the anchors 30.

In one aspect, as shown in FIG. 47, the methodology of delivering theprosthetic valve replacement can further comprise occluding the formedopening in the atrial septum 68 if necessary. Once the septum issuccessfully closed, the delivery catheter 62 can be removed from thebody and the procedure is complete.

In one aspect, the prosthetic valve 12 can be configured to surgicallyreplace a portion of the native valve. The upper flared portion 13 ofthe prosthetic valve 12 can also be configured to situate above thenative annulus and be reinforced by suturing it to the native mitralannulus. In this aspect, it is contemplated that a plurality ofstitches, such as, for example and without limitation, at least 4stitches, at least 6 stitches, at least 8 stitches, and/or at least 4 to10 stitches, are required to be placed within the annulus 4. All suturescan be spaced symmetrically along the posterior annulus 4. All suturescan extend about 1-3 mm from the leaflet-annulus junction or leaflethinge. The first suture can be placed at the cleft between the anteriorleaflet 1 and the posteromedial commissure 5 b. The last suture can beplaced at the cleft between the anterior leaflet 1 and anterolateralcommissure 5 a. Each end of the sutures can then pass through the upperflared portion 13 of the valve. Once all sutures are placed, theprosthetic valve 12 can be deployed in place. All sutures can be tiedonce the prosthetic valve 12 is well positioned.

To further demonstrate the functionality of the prosthetic valvereplacement device and system, ex vivo benchtop tests were performedusing a pig heart. The prototype of the prosthetic valve 12 wasimplanted within the native mitral valve 1,2. The upper flared portion13 of the stent 31 was sewn onto the annulus in an annuloplasty fashion.FIG. 48A shows the prosthetic valve positioned in a passive heart, withno pressure in the left ventricle. The prosthetic leaflets 16 and thenative anterior leaflets 1 were free hanging. The two lateral edges 26a, 26 b of the prosthetic valve were placed at the anterior 5 a andposterior 5 b commissures. The prosthetic valve did not cover thevicinity of the anterior mitral leaflet 1. FIG. 48B shows the prostheticvalve 12 positioned in a pressurized heart, with a pressure rangingbetween 100-120 mmHg within the enclosed left ventricle 10. The maximumpressure was developed using the static pressure test using an elevatedwater tank so that a pressure of 100-120 mmHg could be reached at thelevel of the left ventricle. The aorta was cannulated to allow inflow ofwater into the left ventricle. All three prosthetic leaflets 16 and thenative anterior mitral leaflet 1 were visible upon pressurization. Asshown, the prosthetic valve 12 successfully allowed proper coaptation ofthe leaflets, thereby preventing regurgitant flow. The prostheticleaflets 16 coapted with the native anterior leaflet. A continuouscoaptation line 71, (A1/16 a, A2/16 b, A3/16 c), was visible from thetop view. No paravalvular leakage was observed during pressurization.

To demonstrate the functionality of the locking devices, ex vivo benchtests were performed using a pig heart. Prior to the prosthetic valvedeployment, five anchors 30 were positioned within the mitral annulususing the anchor delivery catheters 48. The prosthetic valve 12 was thencrimped onto a catheter 62 together with the locking assembly. Theprosthetic valve was first released by retracting the valve catheter, asshown in FIG. 49A. Immediately after the valve was released in FIG. 49B,the lock catheters 57 were pushed out instantaneously, as shown in FIG.50A. FIG. 50B was taken after release of the lock devices 70, and apressure of 90 mmHg was applied, showing that the prosthetic valve 12was securely anchored to the mitral annulus.

A surgical proof-of-concept of the device, shown in FIGS. 51A-51D, wasdemonstrated by testing in live animals (i.e., pigs). The primary safetyendpoint was animal health and freedom from death. The secondary safetyendpoint was freedom from device embolization or migration and no totrace mitral regurgitation (MR) grade after implantation at day 7 and30. The primary safety endpoint was met in all tested animals (n=3). Thesecondary safety endpoint was met in two out of three animals. Oneprosthetic valve failure occurred in one animal where an oversizeddevice was used, resulting in 2+MR (a regurgitant jet located at theanterolateral commissure) at day 30, the remaining two animals had traceto no MR and were clinically healthy. Hemodynamic evaluation wasperformed using computed tomography (CT), cardiac fluoroscopy,intracardiac echocardiogram (ICE), and transesophageal echocardiogram(TEE) on each animal after deployment at day 7 and day 30.

CT images consistently showed that the prosthetic leaflets 16 of theprosthetic valve 12 produced proper coaptation 71 with the nativeanterior mitral leaflet 1. The native anterior mitral leaflet 1 isdivided into three scallops, A1, A2 and A3. A1 is at the anterolateralcommissure and A3 is at the posteromedial commissure. The short axisviews of the mitral valve at the level of the mitral annulus, in FIGS.51A, shows the native anterior 1 and posterior leaflets 2 revealed aclear coaptation line. Good coaptation 71 between all prostheticleaflets 16 of the prosthetic valve 12 and of native heart valve leaflet1 were further shown in FIGS. 51B-51D. FIG. 51B shows the nativeanterior leaflet 1 at A2 coapting with the prosthetic posterior leaflet16 b, FIG. 51C shows the native anterior leaflet 1 at A1 coapting withthe prosthetic anterolateral commissure leaflet 16 a, and FIG. 51D showsthe native anterior leaflet 1 at A3 coapting with the prostheticposteromedial commissure leaflet 16 c. The stent frame 31 of theprosthetic valve 12 was clearly visible in these images, showing theupper flared portion 13 and the lower ventricular portion 14 positioningat the annulus 4 and within the left ventricle 10, respectively. Therewas no evidence of damage to the left ventricle from the stent frame ofthe prosthetic valve at 30 days.

Coaptation 71 of the prosthetic leaflets 16 and native leaflet 1 can befurther illustrated in echocardiograms. The echocardiogram of the mitralvalve in systole, FIG. 52, shows that the native anterior leaflet 1 atA2 can coapt with the prosthetic leaflet 16 b and there was noobstruction of the LVOT by the prosthetic valve 12. Cardiac fluoroscopy,as shown in a series of images captured during left ventricularcontraction in FIG. 53, was performed to detect regurgitant flow throughthe mitral valve. Little to no regurgitant volume was observed duringmitral valve closure.

The early feasibility study of the prosthetic valve 12 showed that itcould replicate the function of the native posterior leaflet 2. The datashowed that upon prosthetic valve implantation, there was little to noMR in all but one animal in 30-day study. This prosthetic valve 12 couldbe used to replace the posterior leaflet of valves with MR, includingbut not limiting to, functional class of MR: type I MR with annulardilation or leaflet perforation/tear (normal leaflet motion), type II MRwith papillary muscle and chordae tendineae rupture and/or elongatedchordae tendineae (excessive leaflet motion), type Ma MR with leafletrestriction motion in both diastole and systole due to mitral tissuethickening and fusion, and type IIIb MR with leaflet restriction motionin systole due to left ventricular enlargement leading to apico-lateralpapillary muscle displacement and chordae tethering. Other etiologies ofMR that this prosthetic valve 12 can be used including, but not limitingto, primary or degenerative MR.

It should be emphasized that the above-described aspects are merelypossible examples of implementation, merely set forth a clearunderstanding of the principles of the present disclosure. Manyvariations and modifications can be made to the above-describedembodiment(s) without departing substantially from the spirit andprinciples of the present disclosure. All such modifications andvariations are intended to be included herein within the scope of thepresent disclosure, and all possible claims to individual aspects orcombinations of elements or steps are intended to be supported by thepresent disclosure. Moreover, although specific terms are employedherein, as well as in the claims which follow, they are used only in ageneric and descriptive sense, and not for the purposes of limiting thedescribed invention, nor the claims which follow.

We claim:
 1. A prosthetic heart valve for replacing a native leaflet ina diseased heart valve, comprising: a stent comprising a frame includingan upper flared portion configured to span at least a portion of anative annulus of the diseased heart valve in an operative position, anda lower ventricular portion configured to span only a portion of thenative annulus and allow for dynamic motion of at least one nativeleaflet in the operative position; at least one prosthetic leafletextending inward radially from an inner surface of the frame, whereinthe at least one prosthetic leaflet is configured to be moveable from anopen to a closed position during a cardiac cycle in the operativeposition; a sealing skirt attached to at least one portion of the frame;and at least one dual-guiding-and-fixation member comprising at least aportion configured to embed in native tissue and at least a portionconfigured to selectively engage the frame to guide the frame to, andfix the frame relative to the native annulus in the operative position.2. The prosthetic heart valve of claim 1, wherein the stent isselectively expandable from a compressed position to an expanded,operative position.
 3. The prosthetic heart valve of claim 1, wherein,in the operative position, the upper flared portion covers the entirecircumference of the native annulus of the diseased heart valve.
 4. Theprosthetic heart valve of claim 1, wherein the upper flared portioncomprises at least one opening extending through the upper flaredportion configured to allow at least a portion of at least one anchortether to pass therethrough to guide the prosthetic heart valve duringdeployment and/or fixate the upper flared portion to the native annulus.5. The prosthetic heart valve of claim 1, wherein the at least onedual-guiding-and-fixation member comprises a plurality ofdual-guiding-and-fixation members, and wherein the upper flared portioncomprises a plurality of openings extending through the upper flaredportion configured to allow at least a portion of, respective anchortethers of the dual-guiding-and-fixation members to pass therethrough toguide the prosthetic heart valve during deployment and/or fixate theupper flared portion to the native annulus.
 6. The prosthetic heartvalve of claim 4, wherein the at least one opening comprises one of acircular, square, diamond, triangle, or asymmetrical shape.
 7. Theprosthetic heart valve of claim 4, wherein the each of the at least oneopening has an open area between about 0.2 mm² to 2 mm².
 8. Theprosthetic heart valve of claim 1, wherein the upper flared portion ofthe frame comprises a mechanism to reduce an annular dimensions of theframe.
 9. The prosthetic heart valve of claim 1, wherein the framedefines a longitudinal axis extending between opposite ends of theframe, and wherein the upper flared portion defines an angle relative tothe lower ventricular portion of the stent along the longitudinal axisbetween ninety and one hundred fifty degrees (90-150°).
 10. Theprosthetic heart valve of claim 1, wherein circumferential regions ofthe lower ventricular portion of the frame have different lengths alongits circumference.
 11. The prosthetic heart valve of claim 1, whereinthe lower ventricular portion of the frame comprises one or morefeatures configured to capture native leaflets of the diseased heartvalve when the stent is operatively positioned relative to the nativeannulus.
 12. The prosthetic heart valve of claim 11, wherein the one ormore features comprise one or more flanges, hooks, coils, or clipsconfigured to capture native leaflets of the diseased heart valve. 13.The prosthetic heart valve of claim 1, wherein the at least oneprosthetic leaflet is configured with at least one prong structure. 14.The prosthetic heart valve of claim 13, wherein the at least one prongstructure comprises a plurality of prong structures.
 15. The prostheticheart valve of claim 1, wherein the lower ventricular portion of theframe comprises a partial cylindrical or partial conical shape.
 16. Aprosthetic heart valve for replacing a native leaflet in a diseasedheart valve, comprising: a stent compressible to a compressed positionduring delivery and expandable to an operative position when deployedwithin a native annulus of the diseased heart valve, the stentcomprising a frame including an upper flared portion configured toextend entirely around a circumference of the native annulus in anoperative position, and a lower ventricular portion configured to extendonly partially around the circumference of the native annulus and allowfor dynamic motion of at least one native leaflet in the operativeposition; at least one prosthetic leaflet extending inward radially froman inner surface of the frame, wherein the at least one prostheticleaflet is configured to be moveable from an open to a closed positionduring a cardiac cycle in the operative position; a sealing skirtattached to at least one portion of the frame; and a plurality ofelongate dual-guiding-and-fixation members, each member comprising afirst portion configured to embed in native tissue on or around thenative annulus, a second portion configured to guide the frame into thenative annulus during delivery, and a third portion to fix the framerelative to the native annulus.
 17. The prosthetic heart valve of claim16, wherein the lower ventricular portion of the frame comprises one ormore features configured to capture native leaflets of the diseasedheart valve when the stent is operatively positioned relative to thenative annulus.
 18. The prosthetic heart valve of claim 16, wherein theat least one prosthetic leaflet is configured with at least one prongstructure.
 19. The prosthetic heart valve of claim 16, wherein the upperflared portion comprises a plurality of openings extending through theupper flared portion configured to allow at least a portion of,respective anchor tethers of the dual-guiding-and-fixation members topass therethrough to guide the prosthetic heart valve during deploymentand/or fixate the upper flared portion to the native annulus.
 20. Aprosthetic heart valve for replacing a native leaflet in a diseasedheart valve, comprising: a stent compressible to a compressed positionduring delivery and expandable to an operative position when deployedwithin a native annulus of the diseased heart valve, the stentcomprising a frame including an upper flared portion configured toextend entirely around a circumference of the native annulus in theoperative position, and a lower ventricular portion configured to extendonly partially around the circumference of the native annulus to coverat least one native leaflet and allow for dynamic motion of at least oneother native leaflet in the operative position; at least one prostheticleaflet extending inward radially from an inner surface of the frame,wherein the at least one prosthetic leaflet is configured to be moveablefrom an open to a closed position during a cardiac cycle in theoperative position; a sealing skirt attached to at least one portion ofthe frame; and a plurality of elongate dual-guiding-and-fixationmembers, each member comprising a first portion configured to embed innative tissue on or around the native annulus, a second portionconfigured to guide the frame into the native annulus during delivery,and a third portion to fix the frame relative to the native annulus.